Crystal structure of the murine cytomegalovirus MHC-I homolog m144

J Mol Biol. 2006 Apr 21;358(1):157-71. doi: 10.1016/j.jmb.2006.01.068. Epub 2006 Feb 9.


Large DNA viruses of the herpesvirus family produce proteins that mimic host MHC-I molecules as part of their immunoevasive strategy. The m144 glycoprotein, expressed by murine cytomegalovirus, is thought to be an MHC-I homolog whose expression prolongs viral survival in vivo by preventing natural killer cell activation. To explore the structural basis of this m144 function, we have determined the three-dimensional structure of an m144/beta2-microglobulin (beta2m) complex at 1.9A resolution. This structure reveals the canonical features of MHC-I molecules including readily identifiable alpha1, alpha2, and alpha3 domains. A unique disulfide bond links the alpha1 helix to the beta-sheet floor, explaining the known thermal stability of m144. Close juxtaposition of the alpha1 and alpha2 helices and the lack of critical residues that normally contribute to anchoring the peptide N and C termini eliminates peptide binding. A region of 13 amino acid residues, corresponding to the amino-terminal portion of the alpha2 helix, is missing in the electron density map, suggesting an area of structural flexibility that may be involved in ligand binding.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CD8 Antigens / metabolism
  • Carbohydrates / chemistry
  • Cell Line
  • Crystallography, X-Ray
  • Gene Expression
  • Histocompatibility Antigens Class I / chemistry*
  • Killer Cells, Natural / metabolism
  • Ligands
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Muromegalovirus / chemistry*
  • Peptides / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Sequence Homology
  • Viral Proteins / chemistry*
  • beta 2-Microglobulin / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • CD8 Antigens
  • Carbohydrates
  • Histocompatibility Antigens Class I
  • Ligands
  • Peptides
  • Tap2 protein, mouse
  • Viral Proteins
  • beta 2-Microglobulin
  • m144 protein, Mouse cytomegalovirus 1

Associated data

  • PDB/1U58